The research to be performed in the Hematology Research Laboratory of the Massachusetts General Hospital is fundamentally concerned with the physiology of bone marrow in health and in certain hematologic diseases, notably leukemia and megaloblastic anemia. The focus of the research in recent years has been on basic biochemical studies on the metabolic role of vitamin B12 in bacteria, specifically with the properties and metabolic role of the cobamide-dependent ribonucleoside triphosphate reductase of Lactobacillus leichmannii. The work now turns in the direction of vitamin B12 and folate metabolism in human blood cells and other animal cells. Studies to be undertaken in the next grant period will deal with: (1) biochemical, physiological, and pathophysiological aspects of folylpolyglutamate synthesis; (2) methyltetrahydrofolate-dependent methylations in health and disease; and (3) the role of transcobalamin II and other factors in promoting the assimilation of cobalamins by mitochondria.